Clarifying the function of acetylcholine (ACh) receptors in the brain promises to have important implications for understanding Alzheimer's disease, addiction to nicotine, learning and memory. The overall goal of this proposal is to determine how ACh affects synapses and to ascertain the consequences of changes in synaptic strength. Initial experiments will be conducted in the hippocampus, a brain region involved in learning and memory. ACh is known to play an important modulatory role in the hippocampus by activating different types of receptors. There are, however, many unanswered questions regarding the mechanisms of the modulation and their physiological consequences. One major goal of the proposal is to clarify the types of synaptic connections that are regulated by ACh to determine the mechanisms of the modulation. Another goal is to determine the ultimate effects of such changes in synaptic strength for conditions that would be encountered in different behavioral states in the brain.